JPH0723306B2 - New patch preparation - Google Patents

Description

TECHNICAL FIELD The present invention is aimed at alleviating skin irritation (rash, redness, edema) and skin disorders (contact dermatitis), and applying to the outer skin excellent in tackiness and adhesiveness. It relates to a patch preparation.

2. Description of the Related Art Conventionally known patches (hardeners) are polymer compounds (for example, natural rubber or styrene-butadiene rubber, polybutadiene rubber, polyisobutylene rubber, polyisoprene rubber, butyl rubber, silicone rubber, styrene-isoprene-styrene rubber). Synthetic rubber such as), tackifier (eg, rosin, dehydrogenated rosin or ester, hydrogenated rosin or ester, tempene resin, petroleum resin, etc.), softener (eg, polybutene, liquid paraffin, process) Oil, castor oil, cottonseed oil, palm oil, coconut oil, beeswax, carnauba wax, lanolin, etc.), filler (eg zinc white, calcium carbonate, titanium dioxide, silicas, white pigments, etc.) It is composed of Among these base components, the bases used as tackifiers and softeners are generally the substances that cause side effects such as skin irritation (rash, redness, edema, etc.) and skin disorders (contact dermatitis, etc.). Is suggested as.
In addition, a patch containing these base components is apt to cause a decrease in tackiness, stickiness, or sagging with a change in temperature, and it is difficult to maintain a constant product quality. Since it is used, it has a strong adhesiveness to the skin and is accompanied by pain during peeling, which causes irritation to the skin and the like.

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention In view of the above technical situation, the present inventors intend to eliminate these drawbacks.

That is, 1) A patch comprising a base component that alleviates side effects such as skin irritation or skin damage.

2) A patch that does not contain a patch-imparting agent and a softening agent that have been used in conventional known techniques.

3) A patch that has excellent tackiness and does not cause stickiness or sagging.

4) A patch with less pain when peeling.

5) A patch with excellent stability of the medicinal component in the base.

6) A patch with excellent release of medicinal components from the base.

7) A patch with well-balanced adhesive properties (adhesive strength, adhesive strength, cohesive strength).

As described above, it is an object of the present invention to develop a patch that satisfies the requirements of 1) to 7) as a patch.

Means for Solving the Problems The present inventors have conducted intensive studies to develop a patch that can satisfy the above requirements 1) to 7), and as a result, have found a patch having the following formulation. .

One invention of the present application relates to a patch comprising a base component composed of a thermoplastic acrylic polymer and a thermoplastic urethane polymer and a medicinal component.
The following one invention in the present application relates to a patch obtained by further adding a metal oxide or an organic metal salt as a crosslinking agent to the patch of the present invention.

The background of the completion of the present invention will be described below.

The present inventors first conducted various studies on thermoplastic acrylic polymer homo-prescriptions, but all of them had too low cohesive force, and when the patch was peeled off from the skin, a part of the composition caused cohesive failure. Defects such as remaining on the skin were seen.
Further, an attempt was also made to preform a thermoplastic urethane polymer alone, but since it has no tackiness and adhesiveness at all, it was necessary to add a tackifier or a softening agent, and this study was abandoned.

Then, the present inventors next examined the compounding formulation of the thermoplastic allyl polymer and the thermoplastic urethane polymer and found that they were preferable as the base component of the patch, and completed one of the present inventions. I did.

In addition, when a method of retaining the tackiness thereof for a long period of time was examined in the above invention, it was surprisingly found that this can be solved by adding a crosslinking agent composed of a metal oxide or an organic metal salt. The following one was completed.

The patch of the present invention is a patch having a novel formulation or compounding composition which has not been published in the literature and was first discovered after intensive studies by the present inventors.

Next, the patch of the present invention will be described in detail.

First, 100 parts by weight of both the thermoplastic acrylic polymer and the thermoplastic urethane polymer are blended. The proportion of the thermoplastic acrylic polymer in 100 parts by weight is 40 to 95 parts by weight, and the proportion of the thermoplastic urethane polymer in 100 parts by weight is 5 to 60 parts by weight.

As the thermoplastic acrylic polymer, a polymer having a molecular weight of 10,000 or more and having a viscosity sufficient for coating at a temperature of 200 ° C. or less is preferable. Ionomer type (a general term for polymers having ionic cross-linking, metal ions are Zn ²⁺ , F
e ²⁺ , Cu ²⁺ , Ba ^2+, etc. are used, and because the three-dimensional ionic bond has the property of moving easily at high temperatures, the strength of the softened material is excellent and the activation energy of flow is large) Which is an acrylic acid-based polymer, and has reversible ion formation between high temperature and low temperature by the addition of O-methoxyaryl acid. For example, trade name "QR-969" (made by Rohm and Haas Co.) or Japanese Patent Publication No. 60-47301 or JP-A No. 58-1.
Examples thereof include the compounds described in Japanese Patent No. 25774.

The thermoplastic acrylic polymer is blended in an amount of 40 to 95 parts by weight, preferably 60 to 90 parts by weight, but if it is blended in an amount of 95 parts by weight or more, the adhesive strength is remarkably enhanced and the peeling is accompanied by pain. It is not preferable because it causes skin irritation and skin disorders. If the amount is less than 40 parts by weight, the adhesive strength will be weak and the adhesive will not function.

Further, the thermoplastic urethane-based polymers are roughly classified into two types, a complete thermoplastic type and an incomplete thermoplastic type. In the present invention, the former complete thermoplastic type urethane polymer is used. . This is a urethane polymer having a hydroxyl group in the terminal group of the molecule and having a linear structure, and a polymer having a main chain formed by the reaction of a polyester and an isocyanate. For example, the product name "ESMOCOL-110 (Desmocoll-
110) ”(manufactured by Sumitomo Bayer Urethane Co., Ltd.).

The blending amount of the thermoplastic urethane polymer is 5 to 60 parts by weight, preferably 10 to 40 parts by weight.

The above is the description of the compounding composition relating to the first invention. Next, the second invention will be described. As described above, the second invention further comprises a crosslinking agent in addition to the composition of the first invention, and the metal oxide or the organic metal salt as the crosslinking agent is zinc oxide, copper oxide, aluminum oxide. ,
Divalent or trivalent metal oxides such as iron oxide, magnesium oxide, barium oxide and manganese oxide, or zinc salicylate, copper salicylate, manganese salicylate, nickel salicylate, zinc acetate, zinc carbonate, manganese benzoate,
Examples thereof include organic metal salts such as magnesium citrate, ferrous acetate, zinc stearate, iron lactate, zinc ammonium salicylate, zinc ammonium carbonate, and zinc ammonium benzoate.

The blending amount of these crosslinking agents is 0.05 to 5 parts by weight, preferably 0.2 to 3 parts by weight. The addition of these cross-linking agents,
It has a favorable effect on the long-term retention of the adhesiveness of the patch of the present invention, the stability of the base, the stability of the medicinal component, the release of the medicinal component from the base, and the like.

Next, the medicinal component may be either local or systemic medicinal effect, as long as it is percutaneously absorbed when the patch is applied to the skin and has a pharmacological effect, and is not particularly limited. Not a thing. The blending amount is 0.01 to 30 parts by weight, preferably 0.01 to 20 parts by weight.

An example of the medicinal component will be described below.

Examples of the medicinal component include salicylic acid, methyl salicylate, glycol salicylate, oxyphenbutazone,
Pentazocine, eptazocine phenazole, mepyrizole, piroxicam, isoxicam, benzydamine, tiaramid, bufexamac, acetaminophenone, ibuprofen, alclofenac, acemethacin, ketoprofen, flurbiprofen, diclofenac, fenoprofen, pirprofen, naproxen, sulindac. Bunoxaprofen, mefenamic acid, tolmethine, methiazinic acid, protizic acid, pranoprofen, sontal, fenbufen, fentiazac, diflunisal, zomepirac, pimeprofen, bendazac, miloprofen, amphenac, suprofen, flufenamic acid butyl, loxoprofen, trifenal Acid, thiaprofenic acid, 4-biphenylacetic acid, butorphanol Oxaprozin and analgesic and anti-inflammatory agents which are ester derivatives thereof and skin stimulants such as l-menthol, camphor, peppermint oil, thymol, nicotinic acid benzyl ester, capsicum extract, capsaicin, codin, estazolam, flurazepam, triazolam, nitrazepam, nimetazepam. , Sleep sedatives such as haloxazolam, flunitrazepam, flurazepam, antispasmodic agents such as scopolamine, scopolamine hydrobromide, hydrocortisone acetate, hydrocortisone, prednisolone acetate, triamcinolone acetonide, dexamethasone phosphate ester, methylprednisolone acetate, dichloridisolone acetate, methylprednisolone acetate. Fluocinolone acetonide, dexamethasone acetate, dexamethasone, fluorometholone, betamethasone sodium phosphate Betamethasone, betamethasone valerate, flumethasone pivalate, beclomethasone propionate, fludroxycortide, hydrocortisone butyrate, betamethasone dipropionate, fluocinonide, clobetasol propionate, diflucortolone valerate, halcinonide, amcinonide,
Corticosteroids such as prednisolone valerate acetate, local anesthetics such as lidocaine, benzocaine, ethyl aminobenzoate, procaine hydrochloride, dibucaine and procaine,
Antihistamines such as diphenhydramine hydrochloride, chlorpheniramine, chlorpheniramine maleate, clemastine fumarate, glycyrrhetinic acid, penicillin, tetracycline, oxytetracycline, chlortetracycline, chloramphenicol, sulfonamide, oxytetracycline, fradiomycin sulfate,
Erythromycin, tetracycline hydrochloride, fradiomycin, leucomycin, cephalosporin, cephalexin, neomycin sulfate, bacitracin, kanamycin, streptomycin, gentamicin, grammidine S, micamycin, colistin and other antibiotics, benzalkonium chloride, nitrofurazone, nystatin, acetoacetate Flufamine, clotrimazole, nalidix, sulfamethizole, tolnaftate, pentamycin, amphotericin B, pyrrolenitrin, undecylenic acid,
Antibacterial and antifungal agents such as miconazole, tricomycin, variotin, halopromidine, dimazole hydrochloride, thioconazole, tolcyclate, sulconazole, oxyconazole, croconazole, isoconazole, keratin softeners such as salicylic acid, moctal, chrysalobin, nitroglycerin, isocisin Tall hexanicotinate, isosorbide dinitrate, nicorandil, cinnarizine, dipyridamole, nifedipine, fernarizine, vasodilators, alprenol, indenolol, oxprenolol,
Arrhythmia agents such as carteolol, bucumol, bufetrol, bupranolol, propranol, pindolol, carbamazepine, clonazepam, teoridadine, diazepam, flunitrazepam, chlorpromazine and other tranquilizers, bleomycin, aclacinomycin, adriamycin, pepreomycin, 5 -Fluorouracil and its derivatives, antineoplastic agents such as mitomycin,
Cardiotonic agents such as digitalis, digoxin, digitoxin, and ubidecarenone, sex hormones such as tetosterone, tetosterone enanthate, triethisterone, methylestrenolone, mestranol, valerate estradiol, ethinylestradiol, ethiazide, cyclopenthiazide, hydrochlorothiazide, benzylhydrochlorothiazide, benzylhydrochlorothiazide. Bendroflumethiazide, penfluthizide,
Diuretics such as polythiazide, meticlotiazide, furosemide, bumetanide, metolazone, mefluside, antihypertensive agents such as reserpine, clonidine, prazosin, guanabenz acetate, arotinolol, nadolol, bunazosin, penbutolol, vitamin A, vitamin D, vitamin E, or other Vitamins and ergocalciferol, cholecalciferol, otatothymine, vitamin agents such as riboflavin butyrate, codin phosphate, salbutamonol, tulobuterol, trimethoxynol,
Immunity with procaterol, tranilast, ketotifen, antitussive antitussives such as flumoterol fumarate, lysozyme and other anti-inflammatory enzyme agents, insulin and other antidiabetic agents, D-penicillamine, bestatin, levamisole, lobenzarit disodium, and platonin. And other colchicines, anticonvulsants, antimalarials, prostaglandins, pancreatic hormones, herbal extracts, antitumor agents (H ₂ receptor antagonists, M ₁ receptor antagonists, etc.) and the like. These medicinal ingredients are used alone or in admixture of two or more.

Furthermore, if necessary, diethylene glycol may be added to the patch of the present invention.
Cole, propylene glycol, triethylene glycol
Glycol, polyethylene glycol, etc.
Rensebacate, N-methyl-2-pyrrolidone, N-me
Tylpyrrolidine-N-oxide, urea, crotamiton,
Azone Distribute one or more solubilizing agents or absorption enhancers such as
You can also combine. In addition, conventionally known fragrances and reinforcing fillers
Agents, stabilizers, anti-aging agents, UV absorbers, antioxidants, etc.
If desired, the additive can be added.

Next, the manufacturing method of the present invention will be described.

First, a thermoplastic polymer consisting of 100 parts by weight of a thermoplastic acrylic polymer (40 to 95 parts by weight) and a thermoplastic urethane polymer (5 to 60 parts by weight) is heated and melted at a temperature of 150 to 170 ° C to obtain a uniform mixture. Stir well to achieve In the second invention, when a cross-linking agent (0.05 to 5 parts by weight) is added,
The temperature is reduced to 130-140 and added. Then set the temperature to 100
After the temperature is lowered to ~ 120 ° C, the medicinal component (0.01 to 30 parts by weight) or other additives are added, and the mixture is sufficiently stirred to be kneaded uniformly to obtain a plaster. Further, the paste is spread and applied on the film so as to have a constant thickness in a hot state where it does not solidify.
Next, it is transferred to a stretchable or non-stretchable support (for example, cloth, nonwoven fabric, synthetic film, etc.), and the plaster surface is covered with a release paper to obtain the patch of the present invention.

EXAMPLES The present invention will be specifically described below with reference to examples.

Example 1 To 70 parts by weight of a thermoplastic acrylic polymer [trade name "QR-969" (manufactured by Rohm and Haas Co.)], a thermoplastic urethane polymer [trade name "Desmocool-11 (Desmocool-11)" was added.
0) ”(Sumitomo Bayer Urethane Co., Ltd.)] 30 parts by weight are added, and the mixture is heated and melted within a temperature range of 150 to 170 ° C. in a separable flask, and stirred for about 10 minutes to mix them uniformly. Next, the temperature is lowered to 100 to 120 ° C., and 6 parts by weight of glycol salicylate and 8 parts by weight of 1-menthol are added to about 10 parts.
The mixture was stirred for a minute to obtain a plaster. The thickness of the plaster on the polyethylene terephthalate film is about 90
It was spread with an applicator so that it became μ. About 15 at room temperature
After leaving still for a minute, it was transferred to a support (nonwoven fabric), and the plaster surface was covered with a release paper to give a patch.

* Thermoplastic urethane polymer [Product name "Desmocol-
110 (Desmocoll-110) "(Sumitomo Bayer Urethane Co., Ltd.)] Composition; mainly cotton-like urethane Physical properties; specific gravity (20 ° C) about 1.2 g / cm ³ Solution viscosity: about 2.5 poises Example 2 Thermoplastic acrylic polymer ( To 80 parts by weight of the same sample as in Example 1, 20 parts by weight of a thermoplastic urethane polymer (the same sample as in Example 1) was added, and 150 to 1 in a separable flask was added.
Heat and melt in the temperature range of 70 ° C, stir for about 10 minutes, and mix to homogeneity. Next, the temperature is lowered to 130 to 140 ° C., 1.5 parts by weight of zinc salicylate as a cross-linking agent is added, and the mixture is further stirred for about 10 minutes to uniformly disperse and then lowered to 100 to 120 ° C., 5 parts by weight of glycol salicylate, 1- Menthol 7
Parts by weight were added and stirred for about 10 minutes to obtain a plaster. Hereinafter, a patch was obtained in the same manner as in Example 1.

Example 3 A patch having the following formulation was obtained according to the method of Example 2.

Thermoplastic acrylic polymer (same sample as Example 1) 90 parts by weight Thermoplastic urethane polymer (same sample as Example 1) 10 parts by weight Zinc salicylate 3 parts by weight Glycol salicylate 4 parts by weight 1-menthol 5 parts by weight Example 4 According to the method of Example 1, a patch having the following formulation was obtained.

Thermoplastic acrylic polymer (same sample as in Example 1) 60 parts by weight Thermoplastic urethane polymer (same sample as in Example 1) 40 parts by weight Glycol salicylate 7 parts by weight 1-menthol 8 parts by weight Example 5 Example A patch having the following formulation was obtained according to the method of 2.

Thermoplastic acrylic polymer (same sample as in Example 1) 60 parts by weight Thermoplastic urethane polymer (same sample as in Example 1) 40 parts by weight Zinc oxide 0.3 parts by weight Methyl salicylate 4.5 parts by weight l-menthol 8 parts by weight Example 6 A patch having the following formulation was obtained according to the method of Example 2.

Thermoplastic acrylic polymer (same sample as in Example 1) 85 parts by weight Thermoplastic urethane polymer (same sample as in Example 1) 15 parts by weight Zinc salicylate 3 parts by weight Indomethacin 3 parts by weight l-Menthol 6 parts by weight Implementation Example 7 A patch having the following formulation was obtained according to the method of Example 2.

Thermoplastic acrylic polymer (same sample as Example 1) 80 parts by weight Thermoplastic urethane polymer (same sample as Example 1) 20 parts by weight Zinc salicylate 1.5 parts by weight Ketoprofen 1 part by weight Example 8 Example 2 A patch having the following formulation was obtained according to the method.

Thermoplastic acrylic polymer (same sample as Example 1) 75 parts by weight Thermoplastic urethane polymer (same sample as Example 1) 25 parts by weight Zinc oxide 1 part by weight Flurbiprofen 3 parts by weight Comparative Example 1 heat To 98 parts by weight of the plastic acrylic polymer (same sample as in Example 1), 2 parts by weight of the thermoplastic urethane polymer (same sample as in Example 1) were added, and 150 to 1 in a separable flask was added.
Heat and melt in the temperature range of 70 ° C, stir for about 10 minutes, and mix to homogeneity. Then lower the temperature to 130-140 ℃,
After adding 3 parts by weight of zinc salicylate and further stirring for 10 minutes to uniformly disperse, the temperature was lowered to 100 to 120 ° C., 5 parts by weight of glycol salicylate and 7 parts by weight of 1-menthol were added,
The paste was obtained by stirring for about 10 minutes. A patch was obtained in the same manner as in Example 1 below.

Comparative Example 2 To 30 parts by weight of a thermoplastic acrylic polymer (same sample as in Example 1), 70 parts by weight of a thermoplastic urethane polymer (same sample as in Example 1) was added, and 150 to 1
Heat and melt in the temperature range of 70 ° C, stir for about 10 minutes, and mix to homogeneity. Next, the temperature is lowered to 100 to 120 ° C., and 3 parts by weight of glycol salicylate and 5 parts of 1-menthol are added.
Parts by weight were added and stirred for about 10 minutes to obtain a plaster. A patch was obtained in the same manner as in Example 1 below.

Comparative Example 3 100 parts by weight of natural rubber, 50 parts by weight of tackifier (rosin resin), 20 parts by weight of plasticizer (liquid paraffin), 10 parts by weight of filler (hydrated silica), antioxidant (phenolic antioxidant) 2 parts by weight of agent) was added to 500 parts by weight of toluene and stirred at room temperature for about 3 hours to obtain a composition. To this, 5 parts by weight of methyl salicylate, 2 parts by weight of glycol salicylate, and 8 parts by weight of 1-menthol were added, and the mixture was further stirred for 30 minutes to obtain a plaster. A patch was obtained in the same manner as in Example 1 below.

Test Example 1 Skin Irritation Test Using four types of Examples 1 and 2, Comparative Example 3 and a commercial anti-inflammatory analgesic patch (natural rubber type, containing methyl salicylate), healthy male
Affixed to the upper back of 30 people for 48 hours. The degree of skin irritation of each person was evaluated 30 minutes and 24 hours after peeling. (In addition, the skin irritation used as a criterion is as follows.) The results are shown in Table 1.

From the above test results, it was found that the patch of the present invention significantly reduces skin irritation (rash).

Test Example 2 Skin Adhesion Test and Adhesion Test Using the patches of Examples 1 to 5 and the patches of Comparative Examples 1 and 2 as test pieces, an adhesion test to the skin (standard state and
Adhesive strength, adhesive strength, after being left at 60 ° C for 3 weeks
A cohesive strength adhesive property test was conducted.

The test method and test results will be described below.

1] Adhesion test to skin A total of 7 types of test products of the patch of Examples 1 to 5 of the present invention and the patch of Comparative Examples 1 and 2 were applied to 30 test subjects (in a standard state and a bag in which test pieces were sealed). 14 patches were placed and allowed to stand in a constant temperature bath at 60 ° C. for 3 weeks, and 14 sheets were applied to the front part of the forearm on the surface of 4 × 4 cm. The adhesion to the skin and the ease of peeling from the skin were evaluated comprehensively.

The adhesiveness to the skin as the criterion is as follows.

⊙ ... Excellent in both adhesiveness and peelability.

∘: There is no particular problem in terms of adhesion and peelability, and there is no problem in practical use.

Δ: There are some problems in either the adhesiveness or the peelability.

X: Both the adhesiveness and the peeling property are poor.

2) Adhesive property test 1) Adhesive force test (probe tack method) The force when the probe having a constant cross-sectional area is brought into contact with the surface of the plaster and separated in the vertical direction is measured. Conditions such as release speed can be changed. As a result of this test, contact time 1.0 second, contact pressure 100 g / cm ² ,
The measurement was performed under the condition that the separation speed was 1.0 cm / sec.

2) Adhesion test (180 degree peel strength method) Attach the test piece to the adherend (Bakelite plate) in a predetermined area, and peel the test piece in the 180 degree direction at a pulling speed of 30 cm / min using an autograph. The force of time was measured.

3) Cohesive strength test (shearing cohesive strength) Bonding the plaster surfaces of the test piece together in a specified area, using an autograph, shift the test piece in opposite directions at a pulling speed of 2 cm / min and measure the force at the time of peeling. did.

The above test results are shown in Table 2 below.

As is clear from the test results in Table 2 above, the patches of Examples 1 to 5 of the present invention have very excellent adhesiveness to the skin and also have a very good balance with respect to adhesive properties, and thus are useful as patches. Is meant.

Actions / Effects As described above, the patch of the present invention has the effect of significantly suppressing the occurrence of side effects such as skin irritation and skin disorders in the skin irritation test. This clearly shows how the selection of the base in the patch formulation is an important factor, which fully supports whether the patch formulation of the present invention is superior to the conventional patch formulation. It is a thing.

In addition, if the balance of adhesive properties (adhesive strength, adhesive strength, cohesive strength) is lost, (1) If the adhesive strength is insufficient, it is difficult to adhere to the skin. (2) If the adhesive strength is too strong, it does not peel off easily. Causes skin irritation and skin damage with time-related pain. (3) If adhesive strength is weak, it easily peels off. (4) If cohesive strength is low, "deviation" may occur after application and The patch of the present invention has a well-balanced physical property in the adhesive property, although defects such as sticking out of the plaster around the periphery and residual of the paste during peeling may occur. It is a patch that fully satisfies the requirements for a dripping and patch. In addition, since the adhesive property is excellent as described above, it also has a very excellent and well-balanced adhesive effect even in the actual adhesion test to the skin.

As described above, the patch of the present invention has excellent actions and effects, and is industrially useful as a medicated patch.

Claims (2)

[Claims] 1. 100 to 100 parts by weight of a base component of a thermoplastic acrylic copolymer and a thermoplastic urethane copolymer, 95 to 40 parts by weight of the thermoplastic acrylic copolymer and 5 of the thermoplastic urethane copolymer. A patch preparation comprising a base component having a blending ratio of up to 60 parts by weight, and a medicinal component being added to the base component. 2. A crosslinking agent comprising a metal oxide or an organic metal salt.
The patch preparation according to claim 1, which comprises 0.05 to 5 parts by weight.